The National Center for Advancing Translational Sciences (NCATS)
seeks to develop a therapeutics discovery pilot program to explore new
therapeutic uses for proprietary drug candidates (Agents) across a broad
range of human diseases. This innovative program will match Agents and
associated data from pharmaceutical company partners with the best ideas for
new therapeutic uses from the biomedical research community.

This FOA encourages X02 pre-applications for the NIH-Industry
Pilot Program: Discovering New Therapeutic Uses for Existing Molecules. The
X02 pre-application is the first step in the application process for RFA-TR-12-004 and RFA-TR-12-005;
applicants must read both of the companion FOAs. The X02 pre-applications
will be evaluated by a panel of outside experts for scientific and technical
merit.

Investigators whose X02 pre-applications are judged to be
the most meritorious will be notified of the opportunity to submit a UH2/UH3 or
UH3 application under the Limited Competition for RFA-TR-12-004 or RFA-TR-12-005.
No awards will be made under this FOA.

Key Dates

Posted Date

June 12, 2012

Open Date (Earliest Submission Date)

July 14, 2012

Letter of Intent Due Date

July 14, 2012

Application Due Date(s)

August 14, 2012 , by 5:00 PM local time of applicant
organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

September 2012

Advisory Council Review

Not Applicable

Earliest Start Date(s)

Not Applicable

Expiration Date

August 15, 2012

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF
424 (R&R) Application Guide, except where instructed to do otherwise
(in this FOA or in a Notice from the NIH Guide for Grants and
Contracts). Conformance to all requirements (both in the
Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

On December 23, 2011, Congress created a new center at
the National Institutes of Health (NIH), the National Center for Advancing
Translational Sciences (NCATS, Public
Law 112-74 (amending the Public Health Service Act, 42 U.S.C. § 287)).
One aspect of the NCATS mission is to focus on developing innovative methods
and tools to reduce or eliminate barriers to drug and diagnostic
development. By developing new methods that can be adopted across the
entire medical product development sector, NCATS will enhance others’ ability
to bring safe and effective products to patients. One important way that
NCATS will do this is to develop innovative public-private partnerships with
pharmaceutical companies and the biomedical research community. To this
end, NCATS has developed the NIH-Industry Pilot Program: Discovering New Therapeutic
Uses for Existing Molecules to match discontinued proprietary drug candidates
from pharmaceutical company partners with the best ideas from the biomedical research
community for new therapeutic uses.

In April 2011, NIH convened an NIH-Industry
Roundtable that included a group of senior leaders and experts from the
pharmaceutical industry, government, academia, and the non-profit sector to
explore opportunities to foster new NIH-industry partnerships that facilitate drug
rescue and repurposing. Some of the challenges that were identified
include: resource implications (the time and resources for a
pharmaceutical company to maintain, update, and organize their compound
libraries for drug rescue and repurposing); patent considerations (off-patent
compounds or compounds whose patents are close to expiring, may not be
attractive to industry because the financial return and market incentives for
the product may be limited); and transactional hurdles related to developing,
negotiating and implementing appropriate legal agreements among the parties,
including addressing such concerns as intellectual property rights and
liability. The Roundtable participants agreed that more can and should be
done to increase engagement and partnerships in drug rescue and repurposing and
to enhance the success of these efforts. In response to one of the recommendations
from the meeting, NCATS has developed the NIH-Industry Pilot Program:
Discovering New Therapeutic Uses for Existing Molecules.

The goal of this NCATS program is to enable therapeutics
discovery research through public-private collaborations between NIH,
pharmaceutical company partners, and the biomedical research community in order
to benefit public health. NCATS is especially interested in identifying
projects that address areas of unmet medical need. NCATS plans to
initiate the research program through this FOA as a pilot with a limited set of
high-quality drug candidates (Agents)
and pharmaceutical company partners. If successful, the program may be
expanded to include additional pharmaceutical and biotechnology company
partners, Agents, and new therapeutics discovery projects.

Objectives
of the Program

The Program intends to crowd-source promising Agents with
the best minds in the biomedical research community to investigate their
potential for use in new therapeutic areas. The goal of the program is to
discover new therapeutic uses for Agents that are ready to move quickly into proof of concept trials in the selected
patient population. Proof of concept trials can include, as examples:
use of the Agents as stand-alone interventions, or as adjunctive interventions
(if there is no evidence of drug-drug interactions with the proposed standard
of care treatment). Strategies to inform the selection of patients for proposed
new uses of the Agents are of interest.

For this FOA, Phase Ib and Phase IIa trials are defined as
follows. Phase Ib trials are defined as studies usually conducted in the
target patient population to establish feasibility (e.g., target engagement, pharmacodynamics/pharmacokinetics
(PD/PK), optimal dosing of the Agent) for a Phase IIa proof of concept trial.
Phase IIa proof of concept trials are defined as studies designed to explore
new hypotheses and to assess whether the Agent demonstrates an early signal of
efficacy in the targeted patient population, typically 150 subjects or less. In
addition to clinical benefit, Phase IIa trials also include assessments of
safety, tolerability, and PD/PK response of the Agent.

Through the Limited Competition for the NIH-Industry Pilot
Program: Discovering New Therapeutic Uses for Existing Molecules FOAs, RFA-TR-12-004 (UH2/UH3) or RFA-TR-12-005 (UH3), investigators will have an opportunity to investigate Agents with known
pharmacologic mechanisms of action for clinical efficacy in new therapeutic areas.
Investigators whose X02 pre-applications are judged to be the most meritorious
will be notified of the opportunity to submit a UH2/UH3 or UH3 application
under the Limited Competition FOAs.

RFA-TR-12-004 (UH2/UH3). The
UH2/UH3 is a single application in two stages. The UH2 (Stage 1) will support
milestone-driven feasibility studies to provide evidence for the biological
relevance of the Agent's pharmacologic mechanism/target in pre-clinical disease
models and/or in Phase Ib clinical trials for a period which varies in time
from three months up to one year. UH2 studies should establish a link between
the Agent's mechanism/target and the biology of the proposed disease. UH2 projects
that have met the scientific milestones and feasibility requirements, as evaluated
by NIH administrative review, will be eligible for rapid transition to the
second UH3 stage. The UH3 (Stage 2) will support milestone-driven Phase IIa proof
of concept trials to assess early signals of efficacy of the Agent as a
therapeutic intervention in the proposed disease population and assess its
potential for further clinical development. The project period for the UH3
stage is up to two years.

RFA-TR-12-005 (UH3). This FOA will
support UH3 Phase IIa proof of concept trials in which no initial feasibility
studies are needed to establish optimal dosing or tolerability of the Agent in
the selected patient population. As in the companion FOA, the UH3 will support
milestone-driven Phase IIa proof of concept trials to assess early signals of
efficacy of the Agent as a therapeutic intervention in the proposed disease population
and assess its potential for further clinical development. The project period
for the standalone UH3 stage is up to two years. If invited to apply to the
Limited Competition FOAs, applicants for the UH3 standalone FOA will need to
justify the rationale and availability of sufficient preliminary/feasibility
data to move directly into a Phase IIa proof of concept trial.

Application
Process

The submission of an X02 pre-application is a necessary
first step in applying for an award under RFA-TR-12-004 or RFA-TR-12-005;
applicants must also read both companion FOAs prior to submitting an X02
pre-application. Pre-applications submitted in response to this FOA will
be evaluated by outside experts. X02 applicants will receive feedback on
the scientific merit, technical feasibility, administration and management
plans, and overall potential of the science proposed. Investigators whose X02
pre-applications are identified as being highly meritorious and relevant to
program priorities will be notified of the opportunity to submit a UH2/UH3 or
UH3 application under RFA-TR-12-004 or RFA-TR-12-005,
respectively. No awards will be made for X02 pre-applications under this FOA.

Proposed studies are anticipated to vary based on the
selected Agent's stage of clinical development and the strength of the evidence
supporting the biological rationale for the proposed therapeutic use. For
instance, it may be possible for an Agent to be taken rapidly into clinical
trials, or pre-clinical studies may be needed to provide evidence for the new
therapeutic use. The applicant's team of investigators should have the appropriate
pre-clinical models in place, the ability to recruit patients for the specified
disease, and experience and expertise in conducting clinical trials with the
proposed disease population to demonstrate feasibility of expeditiously
carrying out the proposed research.

Partnership
Information

NCATS has executed a Memorandum of Understanding (MOU)
with each of the pharmaceutical company partners to provide a framework under
which the specified proprietary Agents will be provided by these partners to
the program awardees. Template agreements have been developed for this Program:
Confidential Disclosure Agreements (CDAs)
and Collaborative Research Agreements (CRAs)
between the pharmaceutical company partner and the applicant. These
template agreements have been developed to streamline interactions among the
parties, expediting the indications discovery efforts. X02 applicants should
consider their willingness to agree to the conditions in the appropriate CRA for the selected Agent prior to submitting a pre-application. The investigator is strongly encouraged
to consult early with their institutional technology transfer or sponsored
research office in order to confirm that the terms and conditions of the CDA
and CRA for the selected Agent are acceptable to their institution. A
successful UH2/UH3 or UH3 application will be contingent on the applicant’s
ability to provide the NIH with documentation of access to the selected Agent
and associated data needed for conducting the proposed pre-clinical studies and
for filing an investigator-sponsored IND in order to conduct the proposed
clinical trials (e.g., an executed CRA or letter from the pharmaceutical
partner).

A technical assistance teleconference will be held on June 25,
2012 from 1:00 to 2:30 PM EST. All prospective applicants are invited to
participate. In order to support the number of participants on the conference
call, participants are encouraged to register by June 22 via e-mail at Therapeutics.Discovery@nih.gov.
Please submit questions to be addressed at this webinar on or before June 22.
Answers to the questions will be available on the NCATS Webinar page after the call.

Please also refer to the FAQ page as an additional source of information about the program.

Section II. Award Information

Funding Instrument

The X02 pre-application submitted in response to this
announcement will not result in an award using any of the traditional NIH
mechanisms. A highly meritorious pre-application will result in notification
of the opportunity to submit a UH2/UH3 or UH3 cooperative agreement
application (i.e., RFA-TR-12-004 or RFA-TR-12-005).
For tracking purposes, each pre-application will be assigned a number that
will use the X02 mechanism.

Application Types Allowed

New

The OER
Glossary and the SF 424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

No awards will be made under this announcement.
Through the associated FOAs, RFA-TR-12-004 and RFA-TR-12-005,
NCATS expects to commit up to $20 million in FY2013 to fund six to eight
awards.

Award Budget

Not Applicable

Award Project Period

Not Applicable

NIH grants policies as
described in the NIH
Grants Policy Statement will apply
to the applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant
organizations are strongly encouraged to start the registration process at
least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal
Investigator(s))

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

For these X02 pre-applications, the PD/PI listed on the X02
pre-application must be the same PD/PI listed on a subsequent UH2/UH3 or UH3
application. For X02 pre-applications proposing multiple PD(s)/PI(s), the
contact PD/PI listed on the X02 pre-application must be the same PD/PI listed
on a subsequent UH2/UH3 or UH3 application. The contact PD/PI is strongly
encouraged to continue the multiple PD(s)/PI(s) leadership identified in the
X02 pre-application if notified of the opportunity to submit a UH2/UH3 or UH3
application.

NIH Intramural Research Program (IRP) investigators are
eligible to apply for the X02 FOA. IRP investigators can apply as PD(s)/PI(s),
as multiple PD/PIs in conjunction with extramural investigators (http://grants.nih.gov/grants/multi_pi/index.htm),
or as collaborators with extramural investigators from the biomedical research community.
For more information, see Section 6, Other Submission Requirements and
Information.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. NIH will not accept any
application that is essentially the same as one already reviewed.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and plan
the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

The forms package associated with this FOA includes all
applicable components, mandatory and optional. Please note that some
components marked optional in the application package are required for
submission of applications for this FOA. Follow all instructions in the SF424
(R&R) Application Guide to ensure you complete all appropriate “optional”
components.

Page Limitations

All page limitations described in the SF424 Application
Guide and must be followed, with the following exceptions or additional
requirements:

For this specific FOA, no Specific Aims page will be included.

For this specific FOA, the Research Strategy section is limited
to 6 pages.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

2. In order to ensure an effective review, the application should
be clearly laid out and well organized.

3. See Section 6, Other Submission Requirements and
Information for additional information.

4. Pre-applications are limited to 6 pages for the Research
Strategy. Do not include a Specific Aims page.

Research
Strategy

Within the 6-page Research Strategy, provide the following
information.

1.
Background & Significance

a. Identify the proposed Agent from among those made
available for this Program that you are interested in using, its known
pharmacologic mechanism of action or target, and the new therapeutic use which
will be investigated.

b. Clearly describe the patient population to be
studied.

c. Provide the scientific rationale for selection of
the Agent and its proposed new therapeutic use.

d. Describe the potential impact of the novel
therapeutic use of the Agent for the disease or disorder.

e. Address the global burden of disease, which
patients may benefit, how they may benefit, how use of the Agent might be
superior to current therapy options, potential for impact on public health.

2.
Preliminary Studies

a. The Preliminary Studies section may contain data
and information that validate feasibility for conducting the proposed studies. The
amount of preliminary data available may depend on the level of previous
investigation for the proposed Agent.

b. Examples may include but are not limited to:

In vitro or in vivo evidence that a specific target/pathway
is involved in the disease pathology.

Evidence of why this pathway may be important in
the disease area under investigation.

3.
Approach

a. Provide a plan to assess the validity of the
biological hypothesis for use of the Agent in the new disease area.

Describe the types of approaches that will be used
and how the results will be used to establish feasibility for moving from the
UH2 to UH3 stage of the project, or in some cases, moving directly into a UH3
Phase IIa proof of concept trial.

b. Provide a timeline as well as the steps required
to determine whether a proposed new use of the Agent can be tested in human
trials.

f. Describe the plan for timely accrual of subjects
that links to the expedited timeline for patient recruitment in the UH3 stage.

For some diseases/conditions, patient accrual may
be limiting and multi-center consortia may be needed to expeditiously carry out
the proposed clinical trials.

4.
Administration and Management

a. Provide an operational plan for managing the pre-clinical
studies and clinical trials necessary to fully develop a new use for the Agent.

Include a plan for managing the necessary
collaborations between and among pre-clinical, clinical, and pharmaceutical
company partners, as well as for IND application, IRB approval, and patient
recruitment.

Explain the proposed contribution of each of the key
participants in achieving the objectives of the project.

It will be important for the PD/PI to describe
experience in meeting milestones.

b. Explain the proposed contribution of each of the administrative
components to achieving the objectives of the program.

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424
(R&R) Application Guide, with the following modification:

A Resource Sharing Plan (Data Sharing Plan, Sharing Model
Organisms, and GWAS Sharing Plan) is not applicable for this FOA.

Appendix

Do not use the Appendix to
circumvent page limits. Follow all instructions for the Appendix as described
in the SF424 (R&R) Application Guide. Appendices are not allowed for this
FOA and will not be accepted. Do not use the other attachments section.

Foreign Institutions

Applicants may have subcontracts with foreign institutions
if they provide novel approaches or patient populations. If included, foreign
(non-US) institutions must follow policies described in the NIH Grants
Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in
advance of the deadline to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants
across all Federal agencies. Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration.

Applicants
are responsible for viewing their application in the eRA Commons to ensure accurate
and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the SF
424(R&R) Application Package. Failure to register in the Commons and
to include a valid PD/PI Commons ID in the credential field will prevent the
successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the Central Contractor Registration (CCR). Additional
information may be found in the SF424 (R&R) Application Guide.

1. Biographical
sketch. Use the sample format on the Biographical Sketch Format Page to prepare
this section. Include biographical sketches of all senior/key personnel and
other significant contributors. Describe the role(s) of each key participant in
the project. The Biographical Sketch may not exceed four pages per person.
This four-page limit includes the table at the top of the first page.

2. Letters of
Support. Include a letter from an appropriate institutional official, generally
a dean or provost, documenting institutional commitment to the project,
including provision of resources, space, and available faculty. Include in the
letter confirmation of the Institution’s willingness to engage in the necessary
negotiations with the pharmaceutical company regarding the terms and conditions
of the template CDA and CRA for the selected Agent. A successful UH2/UH3
or UH3 application will be contingent on the applicant’s ability to provide the
NIH with documentation of access to the selected Agent and associated data
needed for conducting the proposed pre-clinical studies and for filing an
investigator-sponsored IND in order to conduct the proposed clinical trials
(e.g., an executed CRA or letter from the pharmaceutical partner).

3. If multiple institutions are involved in an application, a
letter should come from each institution.

4. Human Subjects
Sections. Do not include any attachments that deal with human subjects even if
human subjects will be involved.

5. Vertebrate Animals. Do not use this attachment even if
vertebrate animals will be involved.

6. Budget: Do not include any budget information.

7. Consortium/Contractual Arrangements. Do not use this
attachment.

8. Multiple PD(s)/PI(s) Leadership Plan: Applications
designating multiple PD(s)/PI(s) must include a Multiple PD/PI Leadership Plan
describing the rationale for choosing the multiple PD/PI approach, and the
governance and organizational structure of the leadership team.

Additional
Instructions for NIH Intramural Research Program (IRP) Applicants

1. IRP investigators
can apply as PD(s)/PI(s), as multiple PD(s)/PI(s) in conjunction with extramural
investigators (http://grants.nih.gov/grants/multi_pi/index.htm),
or as collaborators with extramural academic or biotechnology company
investigators, pending the availability of intramural funds to support the
project.

2. An official letter
from the Scientific Director, which indicates approval of the IRP scientist's
role as PD/PI or as collaborator in the project, must be included as a letter
of support in the submission of the X02 pre-application.

3. If selected, NIH IRP scientists, in conjunction
with their respective technology transfer representative, will need to contact
the pharmaceutical company partner providing the selected Agent made available
through this FOA to: execute a CDA to exchange confidential information, and negotiate a PHS Cooperative Research and Development
Agreement (CRADA), Clinical Trials CRADA,
or other similar type of agreement, to incorporate, as appropriate, the terms
of the CRA.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115, with the following modifications: No post-submission materials will be accepted.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact/priority score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are achieved,
how will scientific knowledge, technical capability, and/or clinical practice
be improved? How will successful completion of the aims change the concepts,
methods, technologies, treatments, services, or preventative interventions that
drive this field? Does the proposed novel use of the Agent have the potential to
affect pharmacologic intervention for a disease or disorder with unmet medical
need? Is there a strong biological rationale for the proposed clinical trials?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD(s)/PI(s), do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project? What are the qualifications, experience, and commitment of the personnel involved in the
proposed project? Do the PD(s)/PI(s) have the scientific and organizational
vision and experience to serve effectively as the Director(s) of a therapeutic discovery
effort? Is there evidence of sufficient management capabilities that include
fiscal administration, personnel management, planning, and budgeting? Does the
investigative team have the requisite competencies and experience with clinical
trials planning, recruitment and execution? Do the PD(s)/PI(s) demonstrate relevant
experience and knowledge of public-private partnerships?

Innovation

Not applicable for this pre-application because of
limited information available at this stage about the proposed Agent.

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed? Have the PD(s)/PI(s) provided an operational plan for managing the necessary
collaborations between and among preclinical and clinical plan investigators,
and the pharmaceutical company partner? Have the PD(s)/PI(s) discussed a plan
for submitting an IND application for the proposed clinical trials, IRB
approval, and patient recruitment? Is there a plan for moving expeditiously to Phase
IIa proof of concept trials once a new therapeutic use has been assessed for
biological validity and feasibility?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements? Is there evidence of institutional commitment to the project? Is
there institutional confirmation that the terms and conditions of the CDA and
CRA for the selected Agent are acceptable to the technology transfer or
sponsored research office (for example, through the letter documenting the
Institution's willingness to enter into the necessary agreements with the
pharmaceutical company partner)? Does the scientific environment indicate the
potential for a multi-disciplinary approach involving teams of investigators?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Protections for Human Subjects

Not Applicable.

Inclusion of Women, Minorities, and
Children

Not Applicable.

Vertebrate Animals

Not Applicable.

Biohazards

Not Applicable.

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign
Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Not Applicable.

Budget and Period of Support

Not Applicable.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s), convened by NCATS, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Will receive a written critique.

Applications will be assigned to NCATS with potential secondary assignment, based on the proposed disease population, to the appropriate NIH Institute or Center.

Investigators
whose X02 pre-applications are identified as being highly meritorious and
relevant to program priorities will be notified of the opportunity to submit a UH2/UH3
application under RFA-TR-12-004 or a UH3
application under RFA-TR-12-005.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD(s)/PI(s) will be able to access his or her Summary Statement (written
critique) via the eRA Commons.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of applicable
NIH grants and cooperative agreements are required to report to the
Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301, 479 and 480 of the Public Health Service Act as amended (42 USC 241, 287 and 287a)
and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.